Publicação
Dry powder formulations for antibiotic pulmonary delivery
| Resumo: | In this work, dry powder formulations (DPFs) containing fusidic acid were produced for the purpose of studying the pulmonary delivery of this drug. As fusidic acid is poorly soluble in aqueous media, this drug was conjugated with two different hydrophilic polymers to increase the bioavailability of the drug. The two hydrophilic polymers used were methoxypolyethylene glycol amine, a commercial product, and poly(2-ethyl-2-oxazoline), that was synthesized by supercritical-assisted CO2 polymerization and then end-capped with ethylenediamine. The conjugation compounds were synthesized in one-pot reaction and in inert atmosphere conditions. The compounds were characterized in relation to their physical-chemical properties (NMR, MS) and their antibacterial properties (against methicillin-resistant Staphylococcus aureus, MRSA JE2, and methicillin-sensitive S. aureus, MSSA ATCC 25923 and UAMS-1, strains). The biological test results indicate that both conjugated compounds have antimicrobial activity, but the fusidic acid has the lower values of minimum inhibitory concentration in all the tested pathogens. Trehalose-leucine dry powders were produced through the Supercritical CO2 Assisted Spray-Drying (SASD) technique, testing different operating conditions such as temperature, pressure and CO2/solution flow ratio. After finding the optimal operation conditions, three trehalose-leucine DPFs were prepared, containing fusidic or one of two conjugated compounds. All DPFs were characterized in relation to their morphology (Morphologi G3, SEM), to their physical-chemical properties (FT-IR, Water Content, Quantification of fusidic acid) and aerodynamic performance (Andersen Cascade Impactor measurements - to obtain data such as the fine particle fraction (FPF), emitted fraction (EF) and the mass median aerodynamic diameter (MMAD)). The resulting microparticles showed aerodynamics diameters between 1 and 7 μm, yields up to 67% and FPF up to 62%, making them suitable for pulmonary delivery. |
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| Autores principais: | Morais, Guilherme Mota Horta |
| Assunto: | fusidic acid conjugation reaction dry powders supercritical assisted spray-drying |
| Ano: | 2018 |
| País: | Portugal |
| Tipo de documento: | dissertação de mestrado |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade Nova de Lisboa |
| Idioma: | inglês |
| Origem: | Repositório Institucional da UNL |
| Resumo: | In this work, dry powder formulations (DPFs) containing fusidic acid were produced for the purpose of studying the pulmonary delivery of this drug. As fusidic acid is poorly soluble in aqueous media, this drug was conjugated with two different hydrophilic polymers to increase the bioavailability of the drug. The two hydrophilic polymers used were methoxypolyethylene glycol amine, a commercial product, and poly(2-ethyl-2-oxazoline), that was synthesized by supercritical-assisted CO2 polymerization and then end-capped with ethylenediamine. The conjugation compounds were synthesized in one-pot reaction and in inert atmosphere conditions. The compounds were characterized in relation to their physical-chemical properties (NMR, MS) and their antibacterial properties (against methicillin-resistant Staphylococcus aureus, MRSA JE2, and methicillin-sensitive S. aureus, MSSA ATCC 25923 and UAMS-1, strains). The biological test results indicate that both conjugated compounds have antimicrobial activity, but the fusidic acid has the lower values of minimum inhibitory concentration in all the tested pathogens. Trehalose-leucine dry powders were produced through the Supercritical CO2 Assisted Spray-Drying (SASD) technique, testing different operating conditions such as temperature, pressure and CO2/solution flow ratio. After finding the optimal operation conditions, three trehalose-leucine DPFs were prepared, containing fusidic or one of two conjugated compounds. All DPFs were characterized in relation to their morphology (Morphologi G3, SEM), to their physical-chemical properties (FT-IR, Water Content, Quantification of fusidic acid) and aerodynamic performance (Andersen Cascade Impactor measurements - to obtain data such as the fine particle fraction (FPF), emitted fraction (EF) and the mass median aerodynamic diameter (MMAD)). The resulting microparticles showed aerodynamics diameters between 1 and 7 μm, yields up to 67% and FPF up to 62%, making them suitable for pulmonary delivery. |
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